Statin Therapy for Preventing Recurrent Stroke in Patients with Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Observational Cohort Studies

Abstract

<b><i>Introduction:</i></b> Statins are effective in preventing vascular disease and are widely recommended and used for the secondary prevention of ischemic stroke. However, there is concern from trials that statins might increase the risk of hemorrhagic stroke, partially reducing their benefit. We sought to systematically review the latest evidence on this question. <b><i>Methods:</i></b> Four electronic databases were searched to identify published randomized controlled trials (RCTs) and observational cohort studies (search date December 2020). Two independent reviewers carried out the eligibility assessment based on predefined inclusion criteria. We examined the outcomes of recurrent stroke (after ischemic stroke) of any type, and separately recurrent ischemic stroke and recurrent hemorrhagic stroke. RCTs and observational cohort studies were meta-analyzed separately. Odds ratios (ORs) were used to assess the effect of statin therapy. Meta-analysis was conducted using RevMan 5.4 software. <b><i>Results:</i></b> We retrieved 559 papers in searches, of which 11 RCTs and 12 observational cohort studies were included. Both RCTs and observational studies found that statins reduced the odds of stroke of any type in those with an initial ischemic stroke (11 RCTs: OR = 0.87, 95% CI [0.77,0.97]; <i>p</i> = 0.02; 12 cohort studies: OR = 0.80, 95% CI [0.66, 0.96]; <i>p</i> = 0.02). Both RCTs and observational studies found that recurrence of ischemic stroke was reduced by statins (6 RCTs: OR = 0.81, 95% CI [0.70, 0.93]; <i>p</i> = 0.002; 3 observational studies: OR = 0.67, 95% CI [0.61, 0.75]; <i>p</i> < 0.00001). Data from 7 RCTs and 8 cohort studies did not find a significant difference in hemorrhagic stroke but could not rule out a substantial increase or reduction (7 RCTs: OR = 1.15, 95% CI [0.62, 2.13]; <i>p</i> = 0.66; 8 cohort studies: OR = 0.93, 95% CI [0.71, 1.21]; <i>p</i> = 0.59). <b><i>Conclusions:</i></b> In people who have experienced an ischemic stroke, statins reduce the risk of recurrent stroke of any type medicated through a reduction of ischemic stroke. We found no increase in the risk of hemorrhagic stroke.

Navigating the Statin Landscape: A Comprehensive Review of Stroke Prevention Strategies

“…A meta-analysis of randomized controlled trials revealed that statins led to a 20% reduction in the overall incidence of stroke, with an RR reduction of 21% and an absolute risk reduction of 0.9% [ 18 ]. Another comprehensive meta-analysis, incorporating both randomized controlled trials and observational cohort studies, indicated that statins diminished the odds of stroke of any type and recurrence of ischemic stroke [ 25 ]. However, a more recent meta-analysis suggested that statins may not definitively prevent strokes [ 21 ].…”

“…Robust evidence also strongly indicates that statins are associated with a reduced absolute risk of ischemic strokes and cardiovascular events [ 18 ]. In line with these findings, guidelines from the American Heart Association (AHA) and the American Stroke Association (ASA) emphasize the utility of statin therapy for secondary prevention of strokes, particularly in patients with a history of ischemic stroke [ 25 ]. Moreover, statins are now recommended for the primary prevention of ischemic strokes in patients assessed to have a high 10-year risk for cardiovascular events [ 30 ].…”

“…Various intensities of statin therapy, including high-intensity, moderate-intensity, and low-intensity, lead to different reductions in LDL-C levels: ≥50 percent, 30 to 49 percent, and <30 percent, respectively [ 32 ]. The AHA/ASA Guidelines recommend statin therapy for primary stroke prevention in specific cases, with supporting studies aligning with these guidelines [ 25 ]. However, there are limitations to these guidelines, as they mainly demonstrate the benefits of statins in preventing recurrent stroke without providing conclusive evidence for other outcomes, such as ischemic or hemorrhagic stroke [ 25 ].…”

“…The AHA/ASA Guidelines recommend statin therapy for primary stroke prevention in specific cases, with supporting studies aligning with these guidelines [ 25 ]. However, there are limitations to these guidelines, as they mainly demonstrate the benefits of statins in preventing recurrent stroke without providing conclusive evidence for other outcomes, such as ischemic or hemorrhagic stroke [ 25 ]. A study examining the efficacy of statins in preventing hemorrhagic stroke revealed a higher incidence of hemorrhagic stroke, particularly in older patients treated with statins [ 17 ].…”

Lipid-Derived Biomarkers as Therapeutic Targets for Chronic Coronary Syndrome and Ischemic Stroke: An Updated Narrative Review

“…According to guidelines, statins are the first line of treatment in the secondary prevention of IS [80]. By inhibiting HMG-CoA reductase, which is an essential enzyme of the mevalonate pathway, statins decrease the hepatic cholesterol content, leading to the up-regulation of hepatic LDL receptors and LDL clearance [81].…”